OBJECTIVE: Inflammation caused by infiltrating macrophages and T cells promotes plaque growth in atherosclerosis. Cadherin-11 (CDH11) is a cell-cell adhesion protein implicated in several fibrotic and inflammatory diseases. Much of the research on CDH11 concerns its role in fibroblasts, although its expression in immune cells has been noted as well. The objective of this study was to assess the effect of CDH11 on the atherosclerotic immune response. APPROACH AND RESULTS: In vivo studies of atherosclerosis indicated an increase in Cdh11 in plaque tissue. However, global loss of Cdh11 resulted in increased atherosclerosis and inflammation. It also altered the immune response in circulating leukocytes, decreasing myeloid cell populations and increasing T cell populations, suggesting possible impaired myeloid migration. Bone marrow transplants from Cdh11-deficient mice resulted in similar immune cell profiles. In vitro examination of Cdh11^-/- macrophages revealed reduced migration, despite upregulation of a number of genes related to locomotion. Flow cytometry revealed an increase in CD3+ and CD4+ helper T cell populations in the blood of both the global Cdh11 loss and the bone marrow transplant animals, possibly resulting from increased expression by Cdh11^-/-macrophages of major histocompatibility complex class II molecule genes, which bind to CD4+ T cells for coordinated activation. CONCLUSIONS: CDH11 fundamentally alters the immune response in atherosclerosis, resulting in part from impaired macrophage migration and altered macrophage-induced T cell activation.

中文翻译：

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动脉粥样硬化免疫反应中 cadherin-11 缺失导致巨噬细胞运输受损和辅助 T 细胞募集增加

目的：由浸润的巨噬细胞和 T 细胞引起的炎症可促进动脉粥样硬化斑块的生长。Cadherin-11 (CDH11) 是一种细胞-细胞粘附蛋白，与多种纤维化和炎症性疾病有关。尽管 CDH11 在免疫细胞中的表达也受到关注，但大部分关于 CDH11 的研究都涉及其在成纤维细胞中的作用。本研究的目的是评估 CDH11 对动脉粥样硬化免疫反应的影响。方法和结果：动脉粥样硬化的体内研究表明斑块组织中 Cdh11 的增加。然而，Cdh11 的整体缺失导致动脉粥样硬化和炎症增加。它还改变了循环白细胞中的免疫反应，减少了骨髓细胞数量并增加了 T 细胞数量，这表明骨髓迁移可能受损。来自 Cdh11 缺陷小鼠的骨髓移植产生了相似的免疫细胞谱。Cdh11的体外检查^-/-尽管许多与运动相关的基因上调，但巨噬细胞显示迁移减少。流式细胞术显示全球 Cdh11 缺失和骨髓移植动物血液中 CD3+ 和 CD4+ 辅助性 T 细胞群增加，这可能是由于主要组织相容性复合物 II 类分子基因的 Cdh11 ^-/-巨噬细胞表达增加所致，其与 CD4+ T 细胞结合以协同激活。结论：CDH11 从根本上改变了动脉粥样硬化的免疫反应，部分原因是巨噬细胞迁移受损和巨噬细胞诱导的 T 细胞活化改变。